Viral and bacterial infections are frequently highly contagious, especially when spread by respiration. The recent reports regarding Sudden Acute Respiratory Syndrome (“SARS”), now known to be caused by a corona virus, are proof of how rapidly an infection can spread when it is transmitted through air contact. Other diseases such as influenza spread by air contact, and rapidly reach epidemic proportions, with high numbers of fatalities in elderly and immunocompromised populations.
SARS is a respiratory illness that has recently been reported in Asia, North America, and Europe. As of Apr. 20, 2003, about 198 suspect cases of SARS and 38 probable cases of SARS had been reported in the United States. In general, SARS begins with a fever greater than 100.4° F. [>38.0° C.]. Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some people also experience mild respiratory symptoms. After 2 to 7 days, SARS patients may develop a dry cough and have trouble breathing.
The primary way that SARS appears to spread is by close person-to-person contact. Most cases of SARS have involved people who cared for or lived with someone with SARS, or had direct contact with infectious material (for example, respiratory secretions) from a person who has SARS. Potential ways in which SARS can be spread include touching the skin of other people or objects that are contaminated with infectious droplets and then touching your eye(s), nose, or mouth. This can happen when someone who is sick with SARS coughs or sneezes droplets onto themselves, other people, or nearby surfaces. It also is possible that SARS can be spread more broadly through the air or by other ways that are currently not known. At present there is no treatment or means of prevention for SARS, other than supportive care.
TB, or tuberculosis, is a disease caused by bacteria called Mycobacterium tuberculosis. The bacteria can attack any part of your body, but they usually attack the lungs. TB disease was once the leading cause of death in the United States. In the 1940s, scientists discovered the first of several drugs now used to treat TB. As a result, TB slowly began to disappear in the United States. But TB has come back. Between 1985 and 1992, the number of TB cases increased; more than 16,000 cases were reported in 2000 in the United States.
TB is spread through the air from one person to another. The bacteria are put into the air when a person with TB disease of the lungs or throat coughs or sneezes. People nearby may breathe in these bacteria and become infected.
When a person breathes in TB bacteria, the bacteria can settle in the lungs and begin to grow. From there, they can move through the blood to other parts of the body, such as the kidney, spine, and brain. TB in the lungs or throat can be infectious. This means that the bacteria can be spread to other people. TB in other parts of the body, such as the kidney or spine, is usually not infectious. People with TB disease are most likely to spread it to people they spend time with every day. This includes family members, friends, and coworkers. People who are infected with latent TB do not feel sick, do not have any symptoms, and cannot spread TB, but they may develop TB disease at some time in the future. People with TB disease can be treated and cured if they seek medical help. Even better, people who have latent TB infection but are not yet sick can take medicine so that they will never develop TB disease.
Other human viruses are also highly contagious and have no effective treatments other than containment. For example, Respiratory syncytial virus (RSV) is a very common virus that causes mild cold-like symptoms in adults and older healthy children. RSV is the most common respiratory pathogen in infants and young children. It has infected nearly all infants by the age of two years. It can cause serious respiratory infections in young babies, especially those born prematurely, who have heart or lung disease, or who are immunocompromised. Seasonal outbreaks of acute respiratory illness occur each year, on a schedule that is somewhat predictable in each region. The season typically begins in the fall and runs into the spring. RSV is spread easily by physical contact. Touching, kissing, and shaking hands with an infected person can spread RSV. Transmission is usually by contact with contaminated secretions, called foamites, which may involve tiny droplets or objects that droplets have touched. RSV can live for half an hour or more on hands. The virus can also live up to five hours on countertops and for several hours on used tissues. RSV often spreads very rapidly in crowded households and day care centers.
In infants and young children, RSV can cause pneumonia, bronchiolitis (inflammation of the small airways of the lungs), and tracheobronchitis (croup). In healthy adults and older children, RSV is usually a mild respiratory illness. Although studies have shown that people produce antibody against the virus, infections continue to occur in people of all ages. Each year up to 125,000 infants are hospitalized due to severe RSV disease; and about 1-2% of these infants die. Infants born prematurely, those with chronic lung disease, those who are immunocompromised, and those with certain forms of heart disease are at increased risk for severe RSV disease. Those who are exposed to tobacco smoke, attend daycare, live in crowded conditions, or have school-age siblings are also at higher risk.
Recently, it has been reported that exogenous surfactant supplementation in infants with respiratory syncytial virus bronchiolitis was beneficial (Tibby, et al. Am J Respir Crit. Care Med 2000 October; 162(4 Pt 1): 1251). Infants with RSV bronchiolitis are deficient in surfactant, both in quantity and ability to reduce surface tension. Evidence suggests surfactant has a role in maintaining the patency of conducting airways. Nineteen ventilated infants (median corrected age 4 wk) received either two doses of surfactant (Survanta, 100 mg/kg) within 24 and 48 h of the beginning of mechanical ventilation, or air placebo. Static lung compliance and resistance measured in infants in the placebo-treated group but not in the surfactant-treated group became progressively worse over the first 30 h following enrollment. The principle means of treatment remains supportive however, and there is no means of limiting spread other than isolation.
Influenza is another common viral infection for which there is no effective treatment, and containment is a major option to limit spread of disease. Influenza is caused by three viruses—Influenza A, B and C. Type A is usually responsible for the large outbreaks and is a constantly changing virus. New strains of Type A virus develop regularly and cause new epidemics every few years. Type B causes smaller outbreaks, and Type C usually causes mild illness. In the United States, infection with influenza A and B leads to 20,000 deaths and over 100,000 hospitalizations each year. Influenza is transmitted person to person via contagious droplets that are formed when someone sneezes or coughs. Certain individuals are at higher risk from complications of influenza and therefore vaccination is recommended for these high risk groups. This includes people aged 50 or older, people with diabetes, or with medical conditions affecting the heart, lungs (i.e. asthma) or kidneys; health care workers and anyone with a weakened immune system (HIV, etc.). Supplies of vaccine are limited each year, but after high-risk people have been vaccinated, anyone desiring protection can request vaccination.
Approximately 8 million children and adolescents between 6 months and 17 years of age have one or more medical conditions that put them at increased risk of influenza-related complications. These children should be given the first vaccine available. Such children include those with chronic disorders of the heart or lungs (such as asthma and cystic fibrosis), children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), kidney dysfunction, sickle cell anemia, or immunosuppression. Adolescents who will be in the second or third trimester of pregnancy during the influenza season are another subceptible group that should be vaccinated.
For unvaccinated individuals who have been exposed to people with known influenza, especially if the exposed individual has risk factors, potential use of antiviral medication for more than 2 weeks and vaccination may help prevent illness. For mild illness in people who are not at high-risk, the treatment of influenza is frequently just supportive and includes bed rest, analgesics for muscle aches and pains, and increased intake of fluids. Treatment is usually not necessary for children, but may be prescribed if the illness is diagnosed early and the patient is at risk of progression to more severe disease. Among individuals in high-risk groups (elderly, immunosuppressed, chronic heart, lung or kidney conditions) influenza may be quite severe and can lead to complications.
Epidemics of respiratory infections are not limited to humans. Foot-and-mouth disease virus (FMDV) is the etiologic agent of foot-and-mouth disease (FMD), which is a disease of cattle, swine, and other cloven-footed animals. FMD is characterized by the formation of vesicles on the tongue, nose, muzzle, and coronary bands of infected animals. The virus has several unique characteristics make it one of the most economically devastating diseases in today's world, The ease with which it may be transmitted by contact and aerosol, combined with its enhanced ability to initiate infections, virtually ensures that most, if not all, animals in a herd will contract FMD. The long-term survival of FMDV in infected animals' tissues and organs, especially when refrigerated, offers an opportunity for its national and international transmission through the food chain. Multiple serotypes and numerous subtypes reduce the effectiveness and reliability of vaccines. The possible development of carriers in vaccinated animals and those that have recovered from FMD provides additional potential sources of new outbreaks. These features create a disease that can have a major economic impact on farmers and entire nations. The foot and mouth disease (FMD) epidemic in British livestock remains an ongoing cause for concern, with new cases still arising in previously unaffected areas (Ferguson, et al., Nature 2001 414(6861):329). Epidemiological analyses have been vital in delivering scientific advice to government on effective control measures. Using disease, culling and census data on all livestock farms in Great Britain, the risk factors determining the spatiotemporal evolution of the epidemic and of the impact of control policies on FMD incidence were analyzed. The species mix, animal numbers and the number of distinct land parcels in a farm are central to explaining regional variation in transmission intensity. The parameter estimates obtained in a dynamic model of disease spreading to show that extended culling programs were essential for controlling the epidemic to the extent achieved, but demonstrate that the epidemic could have been substantially reduced in scale had the most efficient methods been used earlier.
Viral shedding is thought to be the mechanism that bioaerosols containing infectious pathogens are generated in one organism and passed to the outside, where they can be inhaled by another animal or human. The devastating consequences that uncontrolled viral shedding can have on livestock were seen in the hoof and mouth disease outbreak in the U.K, where 2030 confirmed cases resulted in the mandatory slaughter of 4 million animals. Recently, more attention is being given to the threat of bioterrorism and the similar risk that a sudden outbreak of disease poses to livestock in the U.S.
Airborne infection is one of the main routes of pathogen transmission in livestock. Aerosols composed of mucus droplet originating in the lungs and nasal cavities are produced when the animal coughs. These bioaerosols can contain pathogens that transmit the disease upon inhalation by exposed animals. Presently, no measures have been taken to redress the potential for the rapid spread of infection by decreasing the rate of bioaerosol production by infected livestock. Such measures would have to carefully consider the physiological mechanism and relevance of bioaerosol production.
It is therefore an object of the present invention to provide a method and formulations for use in decreasing or limiting spread of pulmonary infections, especially viral or bacterial infections.
It is another object of the present invention to provide formulations for treatment of humans or animals to limit infectivity.